Part 1: Key Articles (2011-2018) Your EM Pharmacist Wants You to Know
Authors: Blake Porter, PharmD, BCPS (@RxEmergency, Pharmacist Clinician, Emergency Medicine, University of Vermont Medical Center); Giles W. Slocum, PharmD, BCCCP (@giles_slocum, Emergency Medicine Clinical Pharmacy Specialist, Department of Pharmacy and Assistant Professor, Rush University Medical Center); Nicole M. Acquisto, PharmD, FCCP, FASHP, BCCCP (@nacquisto, Emergency Medicine Clinical Pharmacy Specialist, Department of Pharmacy and Associate Professor, University of Rochester Medical Center); Skyler Lentz, MD (@skylerlentz) // Reviewed by: Alex Koyfman (@EMHighAK) and Brit Long, MD (@long_brit)
Have you ever wondered what your emergency medicine (EM) pharmacist is referring to as you discuss a patient case? Well look no further. In 2018, fourteen EM pharmacists convened to update a previously published review of key articles and guidelines relevant for the EM clinical pharmacist (Thomas 2011, Acquisto 2020). This 52-page updated review systematically identifies and summarizes pertinent research studies and guidelines between 2011 and 2018 related to EM pharmacotherapy. The utility of these articles is not limited to the EM pharmacist; they are relevant to EM physicians, physician assistants, nurse practitioners, and other clinical staff. This review should also prove to be useful for those practicing within urgent care sites, prehospital medicine, and especially for students, residents, and new EM clinicians. In this Part 1, a selection of these key articles and the author takeaways are summarized below. A more detailed discussion is available in the full paper (Acquisto 2020). Part 2 will discuss pertinent guidelines.
Sedation for Mechanical Ventilation
Less is more. Deep levels of sedation in the emergency department (ED) are associated with increased mortality. Post-intubation sedatives should be dose-titrated to achieve a lighter level of sedation in the ED.
- Stephens et al. Analgosedation practices and the impact of sedation depth on clinical outcomes among patients requiring mechanical ventilation in the ED: a cohort study.
Ketorolac 10 mg IV is likely the ceiling dose for renal colic. A dose of 15 mg is appropriate in the United States due to available vial size (e.g. 15, 30, or 60 mg/mL).
- Motov et al. Comparison of intravenous ketorolac at three single-dose regimens for treating acute pain in the emergency department: a randomized controlled trial.
Ibuprofen alone may be effective for pediatric musculoskeletal injury. Use without morphine is associated with less adverse effects.
- Le May et al. Oral analgesics utilization for children with musculoskeletal injury (OUCH Trial): an RCT.
The role of Andexanet alfa compared to prothrombin complex concentrate (PCC) remains unclear for factor Xa-inhibitor reversal.
- Connolly et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors (ANNEXA-4).
Diltiazem may be more effective than metoprolol for heart rate control in atrial fibrillation with rapid ventricular response.
- Fromm et al. Diltiazem vs. metoprolol in the management of atrial fibrillation or flutter with rapid ventricular rate in the emergency department.
Procainamide has advantages like higher rates of tachycardia termination of regular wide QRS complex tachycardia and less major cardiac events and adverse events compared to amiodarone.
- Ortiz et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study.
Early use of long acting insulin in combination with IV insulin for DKA should be considered.
- Doshi et al. Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study.
To avoid IV insulin infusions, rapid-acting subcutaneous insulin should be considered as an alternative for mild to moderate DKA.
Antibiotics in combination with incision and drainage for uncomplicated abscess do not decrease the risk of invasive infection and the benefits may be offset by adverse effects.
- Wang et al. Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis.
Piperacillin/tazobactam plus vancomycin for greater than or equal to 48 hours is associated with increased rates of acute kidney injury (AKI).
- Hammond et al. Systematic review and meta-analysis of acute kidney injury associated with concomitant vancomycin and piperacillin/ tazobactam.
Fluoroquinolones are associated with many adverse effects and should be limited to situations where there are no alternative therapy options.
- Tandan et al. Adverse events of fluoroquinolones vs. other antimicrobials prescribed in primary care: A systematic review and meta- analysis of randomized controlled trials.
Esophageal foreign body
Glucagon has a low success rate with increased risks (e.g. vomiting).
- Bodkin et al. Effectiveness of glucagon in relieving esophageal foreign body impaction: a multicenter study.
Ketamine is a quick-acting option for prehospital management of excited delirium.
- Linder et al. Ketamine for the acute management of excited delirium and agitation in the prehospital setting.
The optimal target blood pressure in intracranial hemorrhage (ICH) is debatable. Institutions should develop consensus recommendations for target range systolic blood pressure (SBP) that is below 180 mmHg.
Metoclopramide and prochlorperazine are first line treatments. Avoid opioids.
- Orr et al. Management of adults with acute migraine in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies.
Reach for IV magnesium in moderate-severe pediatric asthma exacerbations to potentially avoid an admission.
- Su et al. Intravenous and nebulized magnesium sulfate for treating acute asthma in children: a systematic review and meta-analysis.
A single IM dose of corticosteroids in the ED is a reasonable alternative to a short course of oral steroids.
- Kirkland et al. Intramuscular vs oral corticosteroids to reduce relapses following discharge from the emergency department for acute asthma.
Icatibant does not have a role in management of angiotensin converting enzyme (ACE) inhibitor-induced angioedema.
- Sinert et al. CAMEO study group. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema.
Epinephrine does improve survival but may be offset by lack of favorable neurologic outcomes.
- Perkins et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest: PARAMEDIC2 Trial.
No outcome data are available to support push-dose versus continuous infusion pressors in the ED. If used, a standardized process should be developed to ensure safe preparation and administration.
- Holden et al. Safety considerations and guideline-based safe use recommendations for “bolus-dose” vasopressors in the emergency department.
Phenobarbital with or without benzodiazepines is effective and should be considered up front in patients presenting with moderate-severe alcohol withdrawal.
- Mo et al. Barbiturates for the treatment of alcohol withdrawal syndrome: a systematic review of clinical trials.
High dose insulin (1 unit/kg/hr IV) is being increasingly used for severe beta blocker (BB) and calcium channel blocker (CCB) overdose. Institutions should develop processes to ensure safe administration and monitoring of concentrated insulin and dextrose products.
Tranexamic acid (TXA) may reduce mortality and when used in bleeding trauma patients; it should be administered within 3 hours of traumatic injury.
- Roberts et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.
High ratio composition blood transfusion (1:1:1) is associated with a reduced rate of death from exsanguination in severe trauma.
- Holcomb et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs. a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial.
Traumatic Brain Injury
Succinylcholine may be associated with increased mortality in patients with severe head injury.
- Patanwala AE et al. Succinylcholine is associated with increased mortality when used for rapid sequence intubation of severely brain injured patients in the emergency department.
Ketamine is not associated with intracranial pressure (ICP) elevation in patients with traumatic brain injury (TBI).
Above is a selection of pertinent articles this important review summarizes. Whether you are a veteran clinician looking for a concise review or a fresh graduate looking to round out your knowledge base, this review has you covered. We encourage all EM clinicians to peruse this article in the near future. It will help the reader gain a better understanding of the breadth of EM pharmacotherapeutic knowledge available and how to use this information to maintain a strong clinical practice and optimize patient care.
- Thomas MC, Acquisto NM, Patanwala AE, Weant KA, Baker SN. Key articles and guidelines for the emergency medicine pharmacist. Pharmacotherapy. 2011;31(12):1265. doi:10.1592/phco.31.12.1265
- Acquisto NM, Slocum GW, Bilhimer MH, et al. Key articles and guidelines for the emergency medicine clinical pharmacist: 2011-2018 update. Am J Health Syst Pharm. 2020;77(16):1284-1335. doi:10.1093/ajhp/zxaa178
- Stephens RJ, Ablordeppey E, Drewry AM, et al. Analgosedation Practices and the Impact of Sedation Depth on Clinical Outcomes Among Patients Requiring Mechanical Ventilation in the ED: A Cohort Study. Chest. 2017;152(5):963-971. doi:10.1016/j.chest.2017.05.041
- Motov S, Yasavolian M, Likourezos A, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017;70(2):177-184. doi:10.1016/j.annemergmed.2016.10.014
- Le May S, Ali S, Plint AC, et al. Oral Analgesics Utilization for Children With Musculoskeletal Injury (OUCH Trial): An RCT. Pediatrics. 2017;140(5):e20170186. doi:10.1542/peds.2017-0186
- Connolly SJ, Crowther M, Eikelboom JW, et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2019;380(14):1326-1335. doi:10.1056/NEJMoa1814051
- Fromm C, Suau SJ, Cohen V, et al. Diltiazem vs. Metoprolol in the Management of Atrial Fibrillation or Flutter with Rapid Ventricular Rate in the Emergency Department. J Emerg Med. 2015;49(2):175-182. doi:10.1016/j.jemermed.2015.01.014
- Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2017;38(17):1329-1335. doi:10.1093/eurheartj/ehw230
- Doshi P, Potter AJ, De Los Santos D, Banuelos R, Darger BF, Chathampally Y. Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study. Acad Emerg Med. 2015;22(6):657-662. doi:10.1111/acem.12673
- Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Gonzalez-Padilla DA. Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis. Cochrane Database Syst Rev. 2016;(1):CD011281. Published 2016 Jan 21. doi:10.1002/14651858.CD011281.pub2
- Wang W, Chen W, Liu Y, et al. Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis. BMJ Open. 2018;8(2):e020991. Published 2018 Feb 6. doi:10.1136/bmjopen-2017-020991
- Hammond DA, Smith MN, Li C, Hayes SM, Lusardi K, Bookstaver PB. Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam. Clin Infect Dis. 2017;64(5):666-674. doi:10.1093/cid/ciw811
- Tandan M, Cormican M, Vellinga A. Adverse events of fluoroquinolones vs. other antimicrobials prescribed in primary care: A systematic review and meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2018;52(5):529-540. doi:10.1016/j.ijantimicag.2018.04.014
- Bodkin RP, Weant KA, Baker Justice S, Spencer MT, Acquisto NM. Effectiveness of glucagon in relieving esophageal foreign body impaction: a multicenter study. Am J Emerg Med. 2016;34(6):1049-1052. doi:10.1016/j.ajem.2016.03.016
- Linder LM, Ross CA, Weant KA. Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting. Pharmacotherapy. 2018;38(1):139-151. doi:10.1002/phar.2060
- Qureshi AI, Palesch YY, Barsan WG, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016;375(11):1033-1043. doi:10.1056/NEJMoa1603460
- Orr SL, Friedman BW, Christie S, et al. Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2016;56(6):911-940. doi:10.1111/head.12835
- Su Z, Li R, Gai Z. Intravenous and Nebulized Magnesium Sulfate for Treating Acute Asthma in Children: A Systematic Review and Meta-Analysis. Pediatr Emerg Care. 2018;34(6):390-395. doi:10.1097/PEC.0000000000000909
- Kirkland SW, Cross E, Campbell S, Villa-Roel C, Rowe BH. Intramuscular versus oral corticosteroids to reduce relapses following discharge from the emergency department for acute asthma. Cochrane Database Syst Rev. 2018;6(6):CD012629. Published 2018 Jun 2. doi:10.1002/14651858.CD012629.pub2
- Sinert R, Levy P, Bernstein JA, et al. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract. 2017;5(5):1402-1409.e3. doi:10.1016/j.jaip.2017.03.003
- Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018;379(8):711-721. doi:10.1056/NEJMoa1806842
- Holden D, Ramich J, Timm E, Pauze D, Lesar T. Safety Considerations and Guideline-Based Safe Use Recommendations for “Bolus-Dose” Vasopressors in the Emergency Department. Ann Emerg Med. 2018;71(1):83-92. doi:10.1016/j.annemergmed.2017.04.021
- Mo Y, Thomas MC, Karras GE Jr. Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials. J Crit Care. 2016;32:101-107. doi:10.1016/j.jcrc.2015.11.022
- Cole JB, Arens AM, Laes JR, Klein LR, Bangh SA, Olives TD. High dose insulin for beta-blocker and calcium channel-blocker poisoning. Am J Emerg Med. 2018;36(10):1817-1824. doi:10.1016/j.ajem.2018.02.004
- CRASH-2 collaborators, Roberts I, Shakur H, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096-1101.e11012. doi:10.1016/S0140-6736(11)60278-X
- Roberts I, Shakur H, Ker K, Coats T; CRASH-2 Trial collaborators. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev. 2012;12:CD004896. doi:10.1002/14651858.CD004896.pub3
- Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482. doi:10.1001/jama.2015.12
- Patanwala AE, Erstad BL, Roe DJ, Sakles JC. Succinylcholine Is Associated with Increased Mortality When Used for Rapid Sequence Intubation of Severely Brain Injured Patients in the Emergency Department. Pharmacotherapy. 2016;36(1):57-63. doi:10.1002/phar.1683
- Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014;21(1):163-173. doi:10.1007/s12028-013-9950-y